Rafie Carlin, Campa Adriana, Smith Sylvia, Huffman Fatma, Newman Fred, Baum Marianna K
Virginia Commonwealth University, Massey Cancer Center, Richmond, USA.
AIDS Res Hum Retroviruses. 2011 Aug;27(8):815-22. doi: 10.1089/AID.2010.0086. Epub 2011 Jan 15.
Thymulin is a thymic peptide important for the maturation and differentiation of immature thymocytes, which have been found to be depressed in patients with low-level CD4(+) cell recovery despite viral control. Substance use is associated with faster progression of HIV disease, which has been ascribed to poor adherence to antiretroviral medication. Recent findings of an association between cocaine use and decline in CD4(+) cell counts independent of antiretroviral adherence indicate alternative mechanisms for disease progression. We evaluated the relationship between thymulin activity, CD4(+) and CD8(+) cell counts and the CD4(+)/CD8(+) ratio, and the covariate effects of substance use cross-sectionally in 80 HIV(+) active substance users and over 12 months in 40 participants. Thymulin activity was analyzed in plasma using a modification of the sheep rosette bioassay. Thymulin activity was negatively associated with cocaine use (β = -0.908,95% CI: -1.704, -0.112; p = 0.026). Compared to those who do not use cocaine, cocaine users were 37% less likely to have detectable thymulin activity (RR = 0.634, 95% CI: 0.406, 0.989 p = 0.045) and were 75 times more likely to show a decrease in thymulin activity (OR = 74.7, 95% CI: 1.59, 3519.74; p = 0.028) over time. CD4(+) cell count was positively associated with thymulin activity (β = 0.127, 95% CI: 0.048,0.205; p = 0.002), detectable thymulin activity was 2.32 times more likely in those with a CD4 cell count ≥200 cells/μl (RR = 2.324, 95% CI: 1.196, 4.513, p = 0.013), and those with an increase in CD4 cell counts were more likely to show an increase in thymulin activity (OR = 1.02, 95% CI: 1.00, 1.034; p = 0.041) over time. Thymulin activity is predictive of HIV disease progression and is depressed in cocaine users independent of antiretroviral treatment (ART) and HIV viral load. Understanding the mechanisms for accelerated HIV disease progression provides opportunities to find alternative strategies to counteract immunosuppression.
胸腺素是一种对未成熟胸腺细胞的成熟和分化很重要的胸腺肽，已发现在病毒得到控制但CD4(+)细胞恢复水平低的患者中其水平会降低。物质使用与HIV疾病进展加快有关，这归因于对抗逆转录病毒药物的依从性差。最近关于使用可卡因与CD4(+)细胞计数下降之间存在关联的发现表明，疾病进展存在其他机制，且这种关联与抗逆转录病毒治疗的依从性无关。我们对80名HIV阳性的现用物质者进行了横断面研究，对40名参与者进行了为期12个月的研究，以评估胸腺素活性、CD4(+)和CD8(+)细胞计数以及CD4(+)/CD8(+)比值之间的关系，以及物质使用的协变量效应。使用改良的绵羊红细胞花环生物测定法分析血浆中的胸腺素活性。胸腺素活性与可卡因使用呈负相关（β = -0.908，95%可信区间：-1.704，-0.112；p = 0.026）。与不使用可卡因的人相比，使用可卡因的人胸腺素活性可检测到的可能性低37%（相对危险度 = 0.634，95%可信区间：0.406，0.989；p = 0.045），且随着时间推移，胸腺素活性下降的可能性高75倍（比值比 = 74.7，95%可信区间：1.59，3519.74；p = 0.028）。CD4(+)细胞计数与胸腺素活性呈正相关（β = 0.127，95%可信区间：0.048，0.205；p = 0.002），CD4细胞计数≥200个/μl的人胸腺素活性可检测到的可能性高2.32倍（相对危险度 = 2.324，95%可信区间：1.196，4.513；p = 0.013），且随着时间推移，CD4细胞计数增加的人胸腺素活性增加的可能性更大（比值比 = 1.02，95%可信区间：1.00，1.034；p = 0.041）。胸腺素活性可预测HIV疾病进展，且在可卡因使用者中会降低，这与抗逆转录病毒治疗（ART）和HIV病毒载量无关。了解HIV疾病加速进展的机制为寻找对抗免疫抑制的替代策略提供了机会。
